Diabetes Care | 2019
Sickle Cell Trait, European Ancestry, and Longitudinal Tracking of HbA1c Among African Americans: The Jackson Heart Study
Abstract
Studies of differences in glycosylated hemoglobin (HbA1c) have defined race/ethnicity as a social construct (1,2), not using objective biological parameters, and thus comparisons may have been confounded (3). Among blacks without diabetes, we investigated whether the proportion of European genetic ancestry (PEA) mediates the sickle cell trait (SCT) and HbA1c relation and whether PEA tracks HbA1c levels over time accounting for SCT.\n\nWe used data from three Jackson Heart Study (JHS) visits (2000–2004, 2005–2008, and 2009–2013), occurring at 4-year intervals. We excluded participants with diabetes (use of glucose-lowering medication or fasting blood glucose [FBG] ≥126 mg/dL) or prediabetes (FBG ≥100 mg/dL) at visit 1. We estimated PEA using 1,444 ancestry-informative markers. The rs334 variant defined SCT, and rs1050828 indicated glucose-6-phosphate dehydrogenase (G6PD) deficiency. HbA1c was assessed by high-performance liquid chromatography (Tosoh analyzer; assays coefficient of variation 1.4–1.9%).\n\nUsing visit 1 data, we estimated three relations (Fig. 1 A ) corresponding to regressions of 1 ) SCT on HbA1c ( c ), 2 ) SCT on PEA ( a ), and 3 ) both SCT and PEA on HbA1c levels ( c′ ). The indirect effect of PEA on HbA1c was estimated using the difference between c and c′. Complete mediation is observed when c′ = 0 and partial mediation when c − c′ ≠ 0 (Fig. 1 A ).\n\n\n\nFigure 1 \nA : Schematic conceptual framework …